Peptidase is known to relate to various diseases. Dipeptidyl dipeptidase IV (hereinafter sometimes to be abbreviated as DPP-IV), which is one kind of peptidases, is serine protease that specifically binds with a peptide containing proline (or alanine) at the 2nd from the N terminal and cleaves the C-terminal side of the proline (or alanine) to produce dipeptide. DPP-IV has been shown to be the same molecule as CD26, and reported to be also involved in the immune system. While the role of DPP-IV in mammals has not been entirely clarified, it is considered to play an important role in the metabolism of neuropeptides, activation of T cells, adhesion of cancerous cells to endothelial cells, invasion of HIV into cells and the like. Particularly, from the aspect of glycometabolism, DPP-IV is involved in the inactivation of GLP-1 (glucagon-like peptide-1) and GIP (Gastric inhibitory peptide/Glucose-dependent insulinotropic peptide), which are incretins. With regard to GLP-1, moreover, its half-life in plasma is as short as 1–2 minutes, and GLP-1 is known to be degraded by DPP-IV and markedly lose its physiological activity because GLP-1 (9-36)amide, which is a degradation product by DPP-IV, acts on GLP-1 receptor as an antagonist. It is also known that suppression of degradation of GLP-1 by inhibiting activity of DPP-IV leads to potentiation of physiological activity-that GLP-1 shows, such as glucose concentration-dependent insulinotropic effect and the like. From these facts, a compound having a DPP-IV inhibitory activity is expected to show effect on impaired glucose tolerance, postprandial hyperglycemia and fasting hyperglycemia observed in type I and type II diabetes and the like, , obesity or diabetic complications associated therewith and the like.
As therapeutic agents of diabetes now in use, a sulfonylurea, a biguanide, an α-glucosidase inhibitor and the like are known. While a sulfonylurea produce a potent hypoglycemic action, it sometimes causes serious hypoglycemia and requires attention during use. A biguanide easily causes lactic acidosis which is a relatively serious side effect. An α-glucosidase inhibitor delays digestion and absorption of glucose in the gastrointestinal tract and suppresses increase in the blood glucose level after meal, but side effects of sense of distension, diarrhea and the like are problematic (JOSLIN'S DIABETES MELLITUS 13Th Edition 521–522).
Isoquinolone compounds are described in the following publications.    (1) JP-A-7-76573 describes a compound of the formula
wherein ring A and ring B are optionally substituted benzene rings; Q is an oxygen atom or a sulfur atom; R is a hydrogen atom, an optionally substituted hydrocarbon group and the like; W is —CH2OH, —CH2NHR1, —CH2CH2NHR1 (R1 is hydrogen atom or optionally substituted hydrocarbon group) and the like, as a starting material compound of a compound having a calcium antagonistic action and the like, wherein the specific examples are
    (2) Archiv der Pharmazie, vol. 324, pp. 809–814 (1991) describes a compound of the formula
     as a starting material compound of a compound having an anticonvulsant action.    (3) JP-A-7-10844 describes a compound of the formula
     wherein ring A is optionally substituted; ring B is an optionally substituted benzene ring; one of X and Y is —NR1— (R1 is a hydrogen atom, an optionally substituted hydrocarbon group and the like), —O— or —S—, the other is —CO—, —CS— and the like;  is a single bond or a double bond; Z is a carbon atom and the like; D′ is a C1-3 alkylene group; and R5 is a hydrogen atom or an optionally substituted hydrocarbon group] as a starting material compound of a compound having an acyl-CoA cholesterol acyl transferase (ACAT) inhibitory action and the like.
However, there is no report showing that these compounds have a peptidase (preferably DPP-IV) inhibitory activity.
There is a demand on the development of a compound having a peptidase (preferably DPP-IV) inhibitory activity, useful as a prophylactic or therapeutic drug of diabetes and the like and having superior properties in terms of efficacy, duration of action, specificity, low toxicity and the like.